2015 ISCD Position Development Conference
Fracture Risk Prediction by Non-BMD DXA Measures: the 2015 ISCD Official Positions Part 2: Trabecular Bone Score

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Abstract

Bone mineral density (BMD) as measured by dual-energy X-ray absorptiometry (DXA) is the gold standard for the diagnosis and management of osteoporosis. However, BMD explains only 60%–80% of bone strength, and a number of skeletal features other than BMD contribute to bone strength and fracture risk. Advanced imaging modalities can assess some of these skeletal features, but compared to standard DXA, these techniques have higher costs and limited accessibility. A major challenge, therefore, has been to incorporate in clinical practice a readily available, noninvasive technology that permits improvement in fracture-risk prediction beyond that provided by the combination of standard DXA measurements and clinical risk factors. To this end, trabecular bone score (TBS), a gray-level textural index derived from the lumbar spine DXA image, has been investigated. The purpose of this International Society for Clinical Densitometry task force was to review the evidence and develop recommendations on how to incorporate TBS in clinical practice. Clinical applications of TBS for fracture risk assessment, treatment initiation, monitoring of treatment, and use of TBS in special conditions related to greater fracture risk, were addressed. We present the official positions approved by an expert panel following careful review of the recommendations and evidence presented by the TBS task force.

Introduction

Bone mineral density (BMD) as measured by dual-energy X-ray absorptiometry (DXA) is a major determinant of bone strength and fracture risk (1). Currently, a BMD T-score from DXA of −2.5 or less at the lumbar spine (LS), total hip (TH), femoral neck (FN), or one-third radius, allows the diagnosis of osteoporosis in postmenopausal women and in men >50 years old (2). However, although DXA BMD is considered the gold standard for the diagnosis of osteoporosis, most individuals with a fragility fracture will have BMD values in the low bone mass (osteopenic) or even normal range 3, 4, 5. This observation implies that the risk of fracture depends on factors other than BMD.

A number of skeletal features other than BMD, such as bone geometry, microarchitecture, mineralization, bone remodeling, and microdamage contribute to bone strength and overall fracture risk. These features and characteristics of the skeleton that influence a bone's ability to resist fracture are known as bone quality (6). Important aspects of bone quality, namely, bone microarchitecture and bone remodeling, can be assessed in bone biopsies by histomorphometry and micro–computed tomography (7). However, iliac crest bone biopsy is an invasive, not widely available procedure, now used primarily as a research tool. Alternatively, a number of noninvasive imaging modalities, including quantitative computed tomography (QCT), high-resolution peripheral QCT (HRpQCT), and high-resolution magnetic resonance imaging, can measure bone geometry, microarchitecture, and bone strength and distinguish among individuals with and without fragility fracture 8, 9, 10. However, compared to standard DXA, these technologies have higher cost, greater ionizing radiation dose (QCT), and limited accessibility.

In addition to these aspects of bone quality, clinical risk factors for fracture, such as older age, lower body mass index (BMI), family or personal history of osteoporotic fractures, and prolonged glucocorticoid use, increase fracture risk independent of DXA BMD. More important, the combination of clinical risk factors with BMD improves the prediction of fragility fractures compared to BMD alone (11). Based on these findings, a fracture risk assessment tool (FRAX) that assesses clinical risk factors with and without FN BMD, was developed for the prediction of fracture risk and can be used in clinical practice to determine treatment recommendations 12, 13.

A major challenge, therefore, has been to incorporate in clinical practice a readily available, noninvasive technology that permits improvement in fracture-risk prediction beyond that provided by the combination of standard DXA measurements and clinical risk factors. This would allow for a more accurate identification of individuals with greater risk of fracture, improving the cost-effectiveness of treatment. To this end, trabecular bone score (TBS) has been investigated. TBS is a gray-level textural index derived from the LS DXA image that has been previously reported to be associated with fracture risk, partially independent of clinical risk factors and DXA BMD. TBS is measured by dedicated software in the same region of interest as the LS BMD measurement. Although the Food and Drug Administration and the European agency have approved the use of TBS as an adjunct to standard DXA testing, there is no guidance on how to use it in clinical practice. The purpose of this International Society for Clinical Densitometry (ISCD) TBS task force was to review the evidence and develop official positions on how to incorporate TBS in clinical practice.

Section snippets

Background

TBS is a textural index that evaluates pixel gray-level variations in the LS DXA image, providing an indirect index of trabecular architecture (14). TBS is evaluated by determining the variogram of the projected image of the region of interest, calculated as the sum of the squared gray-level differences between pixels at a specific distance. TBS is then calculated as the slope of the log-log transform of this variogram. A dense trabecular structure produces a 2D image with a large number of

Methodology

The ISCD TBS task force reviewed all English language literature available on PubMed. The search term used was “Trabecular Bone Score”, and the search was completed on November 26, 2014. In total, 62 articles were identified and reviewed by the TBS task force. Articles were added as required to enable review of proposed topics. In addition, unpublished or in press articles were reviewed when considered essential to respond to specific questions. The expert panel rated proposed official

ISCD Official Position

  • TBS is associated with vertebral, hip, and major osteoporotic fracture risk in postmenopausal women

  • Grade: Good-B-W

  • TBS is associated with hip fracture risk in men greater than the age of 50 yr

  • Grade: Fair-B-W

  • TBS is associated with major osteoporotic fracture risk in men greater than the age of 50 yr.

  • Grade: Fair-C-W

Postmenopausal Women

In postmenopausal women, 10 cross-sectional studies, all of which were conducted in Caucasian subjects, have shown that LS TBS discriminates between fragility fracture cases and

ISCD Official Position

  • TBS should not be used alone to determine treatment recommendations in clinical practice.

  • Grade: Good-A-W

  • TBS can be used in association with FRAX and BMD to adjust FRAX-probability of fracture in postmenopausal women and older men.

  • Grade: Good-B-W

Rationale

Leslie et al (34) evaluated 33,352 women from the Canadian province of Manitoba, aged 40–100 yr (mean age 63.2 yr). During the mean follow-up of 4.7 yr, 1754 women died and 1872 women sustained at least 1 major osteoporotic fracture (i.e., hip, clinical

ISCD Official Position

  • TBS is not useful for monitoring bisphosphonate treatment in postmenopausal women with osteoporosis.

  • Grade: good-A-W.

Rationale

For a measurement to be useful for monitoring patients in a clinical practice, it must have good precision and an expected change with treatment or clinical status that meets or exceeds the least significant change (LSC). Several studies have reported the precision of TBS measurements compared with the precision of BMD measurements on the same DXA machine (Table 4). The earliest

ISCD Official Position

  • TBS is associated with major osteoporotic fracture risk in postmenopausal women with type 2 diabetes.

  • Grade: Fair-B-L.

Conditions Related to Increased Fracture Risk

A number of studies have evaluated the ability of TBS to discriminate fractured patients from control subjects in various conditions related to increased fracture risk (Table 6). These studies have shown that TBS was associated with fracture risk in the context of diabetes, primary hyperparathyroidism, RA, and adrenal incidentaloma with subclinical hypercortisolism (SH) (Table 6

Summary

In conlcusion, TBS is a gray-level textural index derived from the LS DXA image that is measured by dedicated software in the same region of interest as the LS BMD measurement. Studies in postmenopausal women and older men involving a large number of subjects have consistently shown that low TBS is associated with an increase in both prevalent and incident fragility fractures. The ability of TBS to predict fracture risk is partially independent of central DXA BMD, clinical risk factors, and

Acknowledgments

The authors gratefully acknowledge the assistance of Anne Looker (National Health and Nutrition Examination Survey) in the literature review and Didier Hans (Medimaps) for clarification of technical issues.

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